TR&D 2. Quantitative multi-contrast MRI at 3T and 7T. Principal investigators: Peter C.M. van Zijl, Professor of Radiology Hanzhang Lu, Associate Professor of Radiology SUMMARY The discovery of tissue biomarkers that can provide early and more specific information regarding physiological or metabolic changes can be seen as the holy grail of clinical imaging. The availability of such biomarkers is one of the main issues that we are continuously being inquired about by our collaborative projects (CPs), which study such topics as autism spectum disorder (ASD), pediatric brain development, Attention Deficit Hyperactivity Disorder (ADHD), Alzheimer's Disease (AD), Multiple Sclerosis (MS), Huntington's Disease (HD), Schizophrenia (SCZ), and brain tumors. Our overall goal is therefore to develop MRI methodologies at 3T and 7T that can provide the quantitative biomarkers needed by our CPs. Towards this goal, AIM 1 is focused on the development of exchange transfer imaging (ETI) of the brain. Based originally on chemical exchange saturation transfer (CEST) MRI, which uses pulse sequences similar to conventional magnetization transfer MRI, ETI is broader as it allows the assessment of tissue metabolites that contain exchangeable protons using not only radiofrequency saturation, but instead pulsed excitation sequences that can be used to edit out specific tissue components based on their exchange rate or transverse relaxation time. In addition, we will exploit multi-transmit capabilities of the scanner to avoid amplifier duty cycle limitations on the human scanners. In AIM 2, we will develop methods to determine quantitative magnetic susceptibilities of tissue independent of the orientation of the brain. The purpose of Aim 3 is to design technology that allows assessment of both relative (changes in) and absolute arterial and arteriolar cerebral blood volume (CBVa), venous cerebral blood volume (CBVv), and cerebral metabolic rate of oxygen metabolism (CMRO2).